Irbesartan, 2n-butyl-4-spirocyclopentane-1-[(2′-(tetrazol-5-yl)biphenyl-4-yl)methyl]-2-imidazolin-5 one, can be represented by the following structural formula

Irbesartan is a non-peptide angiotensin-II antagonist. Irbesartan inhibits the action of angiotensin—II on its receptor and thus prevents the increase in blood pressure produced by the hormone—receptor interaction. Irbesartan is, therefore, employed in the treatment of cardiovascular complaints, such as hypertension and heart failure.
U.S. Pat. No. 5,270,317 discloses certain N-substituted heterocyclic derivatives, including 2n-butyl-4-spirocyclopentane-1-[(2′-(tetrazol-5-yl)biphenyl-4-yl)methyl]-2-imidazolin-5 one, and methods of making and using the same.
U.S. Pat. No. 5,629,331 discloses two polymorphic forms, Form A and Form B, of 2n-butyl-4-spirocyclopentane-1-[(2′-(tetrazol-5-yl)biphenyl-4-yl)methyl]-2-imidazolin-5 one, a process for the preparation thereof and uses of the same for the treatment of hypertension.
WO 99/67236 discloses a new crystalline habit of Form A of 2n-butyl-4-spirocyclopentane-1-[(2′-(tetrazol-5-yl)biphenyl-4-yl)methyl]-2-imidazolin-5 one, a process for the preparation thereof and composition containing the same.
WO 03/050110A1 discloses preparation of amorphous 2n-butyl-4-spirocyclopentane-1-[(2′-(tetrazol-5-yl)biphenyl-4-yl)methyl]-2-imidazolin-5 one from Form A and Form B.
WO 04/007482A2 discloses a two phase preparation of irbesartan using a phase transfer catalyst at the trityl irbesartan stage.
WO 04/072064A1 discloses a number of processes for preparing irb-Tr, including reaction of the following starting materials in the presence of a phase transfer catalyst, an inorganic base and a solvent.

The WO2004/072064 process involves isolation of irb-Tr (by separation, column chromatography and, optionally, distillation) before conversion to irbesartan.
There is, however, a need for an improved process for the preparation of irbesartan for the following reasons.
The synthesis of irbesartan as discussed in U.S. Pat. No. 5,270,317, U.S. Pat. No. 5,559,233 and EP 0454511B involves a pre-penultimate reaction step (excluding workup and purification) which comprises reaction of a cyano group on the biphenyl ring with an azide, for example, tributyl tin azide. Reaction times as long as 210 hours are required, see line 5, column 20 of U.S. Pat. No. 5,270,317 and it is recognized in the art that there are safety risks associated with the use of azides.
U.S. Pat. No. 5,629,331 also discloses the reaction of an azide with a cyano group as above, the process being carried out in the presence of a dipolar aprotic solvent, for example, methylpyrrolidone, which is relatively high boiling and can be difficult to remove. U.S. Pat. No. 5,629,331 acknowledges safety risks involved in use of azides at high temperature (see column 4, line 39).
WO Patent 04/007482A2 discloses the preparation of irbesartan using trityl irbesartan in a two phase reaction. Trityl irbesartan is first prepared, isolated in residue form and then detritylated in an acetone —HCl mixture, further basified, filtered with tritanol and reacidified to isolate irbesartan. The isolation of crude irbesartan involves basification, reacidification, toluene distillation and isolation, making the process tedious and unsuitable for use on an industrial scale.
Furthermore, formulation of irbesartan prepared by the above-described prior art processes has required much care because the resulting irbesartan powder tends to stick to the walls of equipment, for example, to the sides of the punches or to the mixer walls, due to its high electrostaticity. There is, therefore, a need for an improved process for the preparation of irbesartan, in particular a process that can provide irbesartan which is non-static, has free flowing properties, shorter reaction time and workup operations, and involves a simplified finishing operation which will enhance productivity and better intrinsic dissolution. This is now essentially achieved by a one-pot process according to the present invention, which results in irbesartan hydrochloride which has excellent flow properties.